Prevalence of presumed ocular tuberculosis among pulmonary tuberculosis patients in a tertiary hospital in the Philippines pdf

This was a cross-sectional study in which 103 patients who were labeled to have active pulmonary tuberculosis underwent history and ocular examination prior to anti-tubercular therapy..

O R I G I N A L R E S E A R C H Open Access

Prevalence of presumed ocular tuberculosis

among pulmonary tuberculosis patients in a

tertiary hospital in the Philippines

Leon Paolo R Lara*and Vicente Ocampo Jr

Abstract

Background: The objective of this study was to determine the prevalence of presumed ocular tuberculosis among diagnosed pulmonary tuberculosis patients in a tertiary government hospital in the Philippines and determine its common presentation in the population This was a cross-sectional study in which 103 patients who were labeled

to have active pulmonary tuberculosis underwent history and ocular examination prior to anti-tubercular therapy The diagnosis of presumed ocular tuberculosis was made when clinical signs of tuberculosis (TB) uveitis were found

in the participants Lesions were documented and tallied, after which statistical analysis was performed

Results: Seven out of the 103 pulmonary TB patients (6.8% prevalence: 95% CI 2.78% to 13.5%) included in the study showed signs of ocular inflammation There was no sex and age predilection between those with presumed ocular TB and those without Posterior uveitis alone was observed in three of the patients (two cases of retinal vasculitis and one case of choroidal tubercle) Non-granulomatous anterior uveitis with posterior synechiae alone was observed in two patients One patient had combined non-granulomatous anterior uveitis with posterior

synechiae and choroidal tubercle One had combined granulomatous anterior uveitis with posterior synechiae and choroidal tubercle Intermediate uveitis was not noted among the patients

Conclusions: Presumed ocular tuberculosis should be considered among patients with diagnosed pulmonary tuberculosis Common ocular lesions found in the study include choroidal tubercle and non-granulomatous anterior uveitis with posterior synechiae

Keywords: Presumed ocular tuberculosis, Prevalence, Anti-tubercular therapy, Extra-pulmonary TB, Anterior uveitis, Posterior uveitis

Background

According to the World Health Organization, the

Philippines ranks fourth in the world for the number

of cases of tuberculosis (TB) and has the highest number

of cases per head in Southeast Asia Almost two thirds of

Filipinos have TB, and up to five million people are

in-fected yearly [1], making it a major public health concern

in the country TB in the Philippines ranked fifth in the 10

leading causes of death and fifth in the 10 leading causes

of illness, with an incidence reported to be 6.3 per

thou-sand per year (culture positive) and 2.6 per thouthou-sand per

year (smear positive) [2] The increased incidence has

economic repercussions not only for the patient's family, but also for the country, with most TB patients belonging

to the economically productive age group (15 to 54 years old) [1]

Though more commonly infecting the pulmonary sys-tem, it can also manifest as extra-pulmonary TB (EPTB) affecting the gastrointestinal, skeletal, cardiac, genitouri-nary, and nervous systems including the eye Diagnosis

of these extra-pulmonary forms is difficult and is often determined by the exclusion of other conditions [3] Some report that it now constitutes a greater proportion of all patients with TB, especially in immunocompromised indi-viduals and the elderly

TB in the eye can manifest in a myriad of ways, and the definitive diagnosis can be daunting due to the dif-ficulty of getting ocular samples for microbiologic or

* Correspondence: paolo_lara@yahoo.com

Department of Ophthalmology, Veterans Memorial Medical Center, North

Avenue, Diliman, Quezon City 1101, Philippines

© 2013 Lara and Ocampo.; licensee Springer This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and

histologic evaluation High awareness of ocular

manifes-tations is a must for an ophthalmologist as he or she

may be the first to diagnose TB [4] A review by Gupta

et al [5] last 2007 updated the clinical spectrum,

la-boratory investigation, and diagnostic criteria that would

assist in the diagnosis of presumed or confirmed

intrao-cular TB so that anti-tuberculous therapy (ATT) can be

initiated on a rational basis

Ocular TB has always been considered rare, yet its

pre-valence has varied widely across time, patient populations,

and geography Some studies include rates of ocular

in-volvement among patients with pulmonary TB (PTB)

Donahue in 1967 reported a prevalence of ocular TB of

1.46% in 10,524 patients from a tuberculosis sanitarium

in the USA [6] A prospective study of Bouza et al from

Spain reported in 1997 examined 100 randomly chosen

patients with proven systemic tuberculosis and found

ocu-lar involvement in 18 patients (18%) [7] In Malawi, Africa,

a 2.8% prevalence of choroidal granuloma in 109 patients

with fever and tuberculosis was reported in a prospective

study in 2002 [8] Biswas and Badrinath examined 2,010

eyes of pulmonary TB patients and found a 1.39% ocular

involvement [9]

Other studies include data about ocular TB as a

frac-tion of uveitis cases It has been estimated to be under

1% in the USA, 4% in China, 6% in Italy, 7% in Japan, and

16% in Saudi Arabia [10] A Southeast Asian neighbor,

Thailand, reported a 2.2% systemic TB involvement [11]

Results

There were 103 patients who were recruited for the

study and who underwent an ocular examination The

mean age was 51.5 years (range 5 to 88), and 62% were

male None of those found to have presumed ocular TB

(POTB) presented with ocular findings on both eyes

Posterior findings

Majority of ocular findings of those found to have POTB

(five eyes of seven people) were located in the posterior

segment Three eyes had a choroidal nodule There were two cases of vascular sheathing consistent with retinal vasculitis, one having a large number of discrete, mostly peripapillary, blot hemorrhages During the 4-week fol-low-up period of the three patients with choroidal tuber-cles, all showed partial clinical resolution with institution

of ATT The two patients exhibiting retinal vasculitis were lost to follow-up

Anterior, intermediate, and other systemic findings

Of the seven patients with presumed ocular TB, four had anterior segment involvement Three exhibited non-granulomatous anterior uveitis with posterior synechiae, one of whom had an incidental chronic peripheral cor-neal degeneration on the involved eye Cervical lympha-denopathy was found in two of these four patients One presented as granulomatous anterior uveitis with posterior synechiae and severe vitritis which was

eventual-ly managed with pars plana vitrectomy Poeventual-lymerase chain reaction (PCR) testing of vitreous aspirate yielded a nega-tive result

All anterior uveitic lesions showed at least partial clini-cal resolution with institution of ATT No signs of inter-mediate uveitis were found Results are summarized in Table 1

Seven out of the 103 pulmonary TB patients (6.8% pre-valence: 95% CI 2.78% to 13.5%) included in the study showed signs of ocular inflammation There was no statis-tically significant difference between the age of those with POTB and those without (p = 0.181; Table 2) Though there were more men (five cases) compared to women (two cases) who had ocular lesions, this was not statisti-cally significant (p = 0.707)

Discussion

We labeled a patient to have ocular TB in this study based on the proposed diagnostic criteria for presumed ocular TB by Gupta et al [5] (i.e., a known clinical sign

of ocular TB with a positive systemic finding such as a

Table 1 Profile of patients labeled to have presumed ocular TB

after 4 weeks

1a 66 M OS: non-GAU with posterior synechiae, choroidal tubercle;

grade 2 cataract, L-cervical lymphadenopathy

0.1/0.050 0.1/0.1 Partial

2 a 68 M OS: GAU, choroidal tubercle, posterior synechiae 0.4/0.025 0.4/0.025 Partial

4 a 36 F OS: non-GAU, posterior synechiae, L-cervical lymphadenopathy 0.67/0.40 0.67/0.50 Partial

Multiple response: Patients 1 and 2 had combined findings in the anterior and posterior segments of the eye; VAi, best-corrected visual acuity (BCVA) prior to ATT;

a

tuberculous lesion on CXR) Though the PCR result

done in one of the seven labeled to have POTB was

negative, it still does not rule out possible ocular TB,

only having a reported maximal sensitivity of 66.6% [12]

Ocular TB is one manifestation of EPTB It can

ad-versely affect the quality of life of people by threatening

vision Of the 103 pulmonary TB patients in the study,

seven (6.8%) showed signs of ocular inflammation There

are probably more cases we were unable to detect

be-cause we did not examine EPTB patients This rate is

higher than the 1.39% to 1.46% ocular involvement found

in other studies [6,9] It can expand the knowledge base

regarding the epidemiology of POTB and can contribute

to greater awareness on the condition

Ocular TB is not easy to diagnose because most of the

time there is no concurrent active systemic TB Notable

in our findings was the unilateral presentation of all

patients labeled as POTB, concurring with the reports of

some authors that ocular TB is usually unilateral [13]

However, the absence of a single manifestation of POTB

further compounds the difficulty in recognizing the

dis-ease In our study, as with other reports [14], posterior

segment lesions were the predominant finding in

pa-tients with POTB This would be a logical finding in our

diagnosed PTB patient population since choroidal

tuber-cles and retinal vasculitis indicate hematogenous seeding

of bacilli EPTB mainly results from reactivation of a

tu-berculous focus after hematogenous dissemination or

lymphogenous spread from a primary, usually pulmonary,

focus [15]

The amount of TB burden necessary in the lungs to

produce EPTB has not yet been quantified TB affects

other sites of the body other than the lungs and eyes

One recently published study found that among the total

of 2,161 TB infection cases, 705 (32.6%) were EPTB,

1,186 (54.9%) were PTB, 106 (4.9%) were disseminated

TB, and 164 (7.6%) were concurrent EPTB-PTB Most common sites of EPTB they found were in pleural (41.1%) and lymphatic (30.6%) tissues followed by ge-nitourinary (7%), bone/joint (5.8%), cutaneous (4.5%), meningeal (4.1%), peritoneal (2.6%), and gastrointestinal (2%) [16] In our study, we incidentally detected two cases of cervical lymphadenopathy out of the seven detected POTB cases

One study conducted a multivariate analysis determi-ning risk factors for developing EPTB relative to PTB, and they found that female gender and older age are associated with EPTB [16] Our male POTB patients outnumbered the females (4:3) However, we found a relatively higher mean age in our POTB cluster, with six

of the seven patients belonging to the 41- to 70-year-old age group We found the mean age of those with POTB higher (60.00 ± 13.760 years old) than those without ocu-lar findings (50.93 ± 17.406 years old) One East Asian study found increasing longevity of their population and the high rate of TB in their elderly as important factors contributing to their persistent high rate of TB [17] Old age has indeed been cited to be a risk factor for EPTB since the immune system can be weaker in the elderly [16,18]

The study is limited by a lack of investigations such as fluorescein angiography, indocyanine green angiography,

or ocular coherence tomography Confounders that com-promise the immune system were not controlled in the analysis (e.g., DM, HIV) Effect modifiers such as cataract were not controlled Future studies could look at the cli-nical/radiological spectrum of PTB cases associated with POTB Since active PTB can easily be genotyped, geno-typic profiling of these cases can also be done

Conclusions Putting things together, an ocular examination before ATT in newly diagnosed TB patients may be beneficial

in our setting for the following reasons: the

relative-ly high (6.8%) prevalence of ocular involvement in TB patients found, the possibility of blindness caused by POTB lesions, and the potential toxicity of some ATT drugs Ultimately, the ophthalmologist and internist should increase their awareness and understanding of

TB and its possible ocular involvement because the dis-ease is curable and blindness is preventable [7]

Methods The study recruited patients diagnosed to have active PTB from August 2010 to September 2011 at a ter-tiary government hospital in the Philippines Patients with respiratory (cough > 2 weeks, hemoptysis, chest pain, breathlessness, etc.) or constitutional symptoms (fever, night sweats, fatigue, loss of appetite, etc.) were

Table 2 Age distribution of study participants

Age

(years)

No ocular TB With ocular TB Total

Mean ± SD 50.93±17.406 60.00±13.760 51 to 544±17.28

p = 0.181; independent t test.

seen and examined by the hospital's pulmonology

ser-vice A chest X-ray is requested, and if a tuberculous

lesion was found, three sputum samples examined for

acid-fast bacilli (AFB) were requested Patient was

la-beled to have active pulmonary TB when AFB smear

was positive If doubt existed about TB presence due

to negative AFB smear result, the hospital's TB

Diag-nostic Committee evaluated the case to judge whether

to label it as active or not

All patients diagnosed to have active pulmonary TB

were referred to the hospital's Department of

Ophthal-mology prior to start of ATT, and a single examiner

evalu-ated the patients They were examined for best-corrected

visual acuity, intraocular pressure, eye movements,

ante-rior segment pathology, and pupillary reactions The

fun-dus was examined by indirect ophthalmoscopy Patients

with history of ocular trauma and previously diagnosed

retinal or optic nerve diseases were excluded from the

study

Signs of TB uveitis were searched for, namely,

non-granulomatous anterior uveitis with posterior synechiae,

granulomatous anterior uveitis, iris nodules, ciliary

bo-dy tuberculoma, granulomatous intermediate uveitis,

in-termediate organizing exudates, choroidal tuberculoma,

subretinal abscess, serpiginous-like choroiditis, retinitis/

vasculitis, optic neuropathy, and endophthalmitis To

la-bel a subject as having POTB, we employed the

Diag-nostic Criteria of Ocular TB proposed by Gupta et al [5]

(Additional file 1) All positive findings were re-assessed

and confirmed by a single uveitis specialist Patients

whose first examination was not suggestive of ocular

in-volvement were not evaluated further Patients with

evi-dence of ocular TB involvement were followed-up after

4 weeks and were labeled to have partial response if

showing clinical improvement of ocular lesions during

this time period

A target number of 101 subjects was set on a 95%

con-fidence level and power was set at 80%, and relative

error of 15% and assumed ocular TB prevalence of 18%

among diagnosed tuberculosis patients were based on

the report by Bouza et al [7] Frequency of findings was

tallied, and significance was assessed by various

statis-tical analyses with alpha set at 0.05 A hospital research

committee approved the study, and the tenets of the

Declaration of Helsinki were observed

Additional file

Additional file 1: Proposed diagnostic criteria of ocular TB by

Gupta et al [5].

Competing interests

The authors report no conflicts of interest The authors alone are responsible

Authors ’ contributions

PL carried out the coordination with the pulmonology department as well as the eye exam of the participants He also drafted the manuscript VO examined participants suspected to have presumed ocular TB and was the one to confirm a patient as having presumed ocular TB He also gave invaluable expert advice throughout the course of the study Both authors read and approved the final manuscript.

Received: 3 September 2012 Accepted: 12 September 2012 Published: 3 January 2013

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doi:10.1186/1869-5760-3-1 Cite this article as: Lara and Ocampo et al.: Prevalence of presumed ocular tuberculosis among pulmonary tuberculosis patients in a tertiary hospital in the Philippines Journal of Opthalmic Inflammation and Infection 2013 3:1.